Pallister-Killiam syndrome symptoms, causes, treatment

The Pallister-Killian syndrome, Also known as tetrasomy 12, it is a rare disease of genetic origin that is characterized by a wide spectrum of multi-organ involvement.

Clinically, this pathology is defined by intellectual disability, psychomotor retardation, muscular hypotonia, an atypical facial phenotype, pigmentary abnormalities in the skin, and alopecia. In addition, other types of medical complications related to malformations in different body systems or seizures may also appear..

The etiological origin of this disease is associated with a genetic disorder distributed in mosaic. Specifically, it is due to the presence of an extra chromosome 12 in some cells of the body.

The diagnosis of Pallister-Killiam syndrome can be made both prenatally and postnatally. The main objective is the identification of the clinical characteristics and the use of a confirmatory genetic study..

This syndrome has a high mortality rate. However, the pharmacological medical approach and rehabilitative treatment can provide important benefits in the quality of life and the clinical status of those affected.

Article index

• 1 History
• 2 Characteristics of Pallister-Killiam syndrome
• 3 Statistics
• 4 Symptoms
  • 4.1 -Facial configuration
  • 4.2 -Muscle-skeletal malformations
  • 4.3 -Muscle hypotonia and psychomotor retardation
  • 4.4 -Neurological disorders
  • 4.5 -Other anomalies
• 5 Causes
• 6 Diagnosis
• 7 Treatment
• 8 References

Story

This disease was initially described by Pallister in 1977. In the first publications, this researcher reported two cases of adult patients whose course was characterized by various findings: seizures, muscular hypotonia, intellectual deficit, musculoskeletal and organic malformations, configuration rough facial and changes in skin color.

In parallel, Teschler-Nicola and Killiam in 1981 described this same clinical picture in a three-year-old girl.

Therefore, in the first clinical reports, a general reference was made to a medical condition characterized by the combination of seizures, intellectual disability and a characteristic physical phenotype..

In addition, already in 1985 Gilgenkratz was able to identify in the first case during the gestation phase, something common today thanks to modern diagnostic techniques.

Characteristics of Pallister-Killiam syndrome

Pallister-Killiam syndrome is a type of genetic mosaic disease. In this case, the chromosomal alteration only affects some cells of the body. A wide involvement of different body systems and organisms is identified.

It is mainly characterized by intellectual disability, muscular hypotonia, the development of distinctive facial features, alteration of skin pigmentation or hair growth, among other congenital alterations..

In addition, Pallister-Kiliam syndrome is a rare disease of congenital origin that can receive a wide number of names in the medical literature:

• Mosaic Pallister-Killiam syndrome.
• Isochromosome 12p syndrome.
• Killiam syndrome.
• Nicola-Teschler syndrome
• Pallister mosaic syndrome.
• Tetrasomy 12p.
• Killiam-Tescheler-Nicola syndrome.

Statistics

Prevalence figures for Pallister-Killiam syndrome are not precisely known. Not many definitive diagnoses have been made and most of these have not been published in the medical literature.

Thus, all authors and institutions define this syndrome as a rare or infrequent genetic pathology in the general population..

About 15 years ago, Pallister-Killiam syndrome had been identified in just about 100 cases worldwide. Currently, this figure has exceeded 200 affected.

Epidemiological investigations have estimated the incidence of this disease at about 5.1 cases per million newborn children, although authors such as Toledo-Bravo de la Laguna and collaborators place it at 1 / 25,000.

A higher prevalence associated with the sociodemographic characteristics of those affected has not been identified. Pallister-Killian syndrome can appear in any gender or technical and / or racial group.

Symptoms

A wide variety of signs and symptoms can be identified in the clinical course of Pallister-Killian syndrome. All of them associated with craniofacial and / or musculoskeletal anomalies and cognitive alterations.

-Facial configuration

The development of cranio-facial malformations from the gestation phase to postnatal and infant growth constitutes one of the most characteristic medical signs of Pallister-Killiam syndrome..

The most common signs and symptoms include abnormalities in the different cranial and facial structures that will lead to a rough and atypical appearance:

• Brachycephaly: This term refers to a cranial configuration that results in an increase in the width of the head and a flattening of the occipital and posterior areas..
• Frontal cranial configuration: the anterior and frontal areas of the head tend to develop more than usual. A prominent or bulging forehead may be seen.
• Posterior cranial configuration: the most posterior area of ​​the head sounds to present an underdeveloped state. A flat occiput can be seen.
• Hypertelorism: the eyes tend to be at a greater distance than usual. Visually, the eyes are widely separated.
• Nasal configuration: the nose usually presents a wide volume, with a wide root or bridge. The nostrils tend to face forward (anteverted nostrils).
• Buccal and maxilla configuration: oral structures tend to be abnormal in size. The jaw is smaller than usual (micrognathia). The upper lip takes on a thin and reduced appearance, while the lower lip is thick. The tongue is larger than expected and the nasolabial fold is long.
• Auditory pinna: ears are lowered and turned back.
• Alopecia: hair growth is abnormal in various areas. The most common is to observe small areas of baldness on the eyebrows, eyelashes or head.
• Achromic and hyperchomic spots: It is possible to identify the development of small spots in facial areas. They are characterized by loss of color or by a dark appearance.

-Musculoskeletal malformations

Despite being less significant than facial alterations, it is very common to observe several musculoskeletal abnormalities in patients affected by Pallister syndrome:

• Neck: the distance between the head and the body trunk is usually reduced. At a visual level we can observe a short or smaller neck than usual.
• Spine: Although it is not very common to identify spinal alterations, it is possible that spina bifida, sacral appendix, scoliosis or kyphosis may appear.
• Extremities: the arms and legs also show abnormal growth, being smaller than expected for the sex and biological age of the affected person.
• Polydactyly: Alterations related to the number of fingers and toes may also appear. The most common is to observe more fingers on the hands

-Muscle hypotonia and psychomotor retardation

Abnormalities related to muscle structure and mobility are another of the cardinal clinical features of Pallister-Killian syndrome:

Muscle hypotonia refers to the identification of abnormally reduced muscle tone or tension. At a visual level, flaccidity and lability can be observed in different muscle groups, especially accentuated in the extremities..

Thus, muscular and skeletal pathology will cause a significant delay in the acquisition of different motor skills, both in the neonatal and childhood periods..

Although the development periods are variable among those affected, the most common calendar includes the following milestones:

• Sitting- The ability to independently acquire postures, sit or spin with your own body can begin to develop as early as 3 months. However, in people affected by this syndrome it can be delayed until 8 years of age..
• First steps: it is usual for children to start taking their first steps around 12 months, however, in this pathology this evolutionary milestone can be delayed until 9 years of age. In addition, in many cases some compensatory methods such as splints or specialized footwear are essential..

-Neurological disorders

Another of the strongly affected areas is the nervous system. In most cases, the signs and symptoms are mainly related to seizures and intellectual disability:

• Convulsive crisis: the presence and development of unusual, altered, and disorganized neural electrical activity can lead to recurrent events defined by muscle spasms, motor agitation, or lack of consciousness. Brain structure is severely impaired, leading to significant cognitive and tissue impairment.
• Intellectual disability: Although the level of cognitive impairment is variable, in most cases a low or borderline IQ is identified. The areas most affected are psychomotor and linguistics, with some of those affected meeting the clinical criteria for autism spectrum disorder.
• Generalized developmental delay: the rate of learning of the different daily and academic skills is usually slow in most of those affected. Adaptations and specialized school support are usually required.

-Other anomalies

Although they are less frequent, other types of medical complications may also appear:

• Cardiac, gastrointestinal, kidney and genital abnormalities and malformations.
• Auditory stenosis.
• Pulmonary hypoplasia.
• Strabismus and cataracts.
• Reduction of visual and hearing acuity.

Causes

The origin of Pallister-Killian syndrome is associated with a genetic mosaic abnormality on chromosome 12. It only affects the genetic material of some cells of the body.

Chromosomes are part of the nucleus of all cells found in the human body. They are made up of a wide variety of biochemical components and contain the genetic information of each individual..

Human beings have 46 different chromosomes, organized in pairs and numbered from 1 to 23. In addition, at the individual level, each chromosome has a short area or arm called "p" and a long one called "q".

The abnormality affects chromosome 12 and leads to the presence of a chromosome with an abnormal structure, called an isochromosome.

Thus, this chromosome tends to have two short arms instead of one of each p (short) and long (q) configuration..

As a consequence, the presence of extra and / or abnormal genetic material will alter the normal and efficient course of physical and cognitive development of the affected person, giving rise to the clinical characteristics of Pallister-Killian syndrome..

Diagnosis

Pallister-Killian syndrome can be identified during pregnancy or in the postnatal stage, based on the clinical characteristics and the results of different laboratory tests..

During pregnancy, the most commonly used tests are ultrasound scans, amniocentesis, or chorionic villus sampling. In this sense, the analysis of the genetic material of the embryo can offer us a confirmation of this pathology, through the identification of compatible anomalies..

On the other hand, if the diagnosis is made after birth, it is essential:

• Skin biopsy.
• Blood tests.
• Study of blood lymphocytes.
• Fluorescent in situ hybridization.
• Comparative genomic hybridization.

Treatment

No specific therapies have been designed to treat people with Pallister-Killian syndrome..

This syndrome is usually associated with a poor neurological prognosis and high mortality rates. However, rehabilitative treatment, special education and occupational therapy can offer a good functional prognosis and an increase in the quality of life of those affected..

For example, Méndez and his work team (2013) describe a case of rehabilitative treatment characterized by:

• Improvements in psychomotor skills: head control, independent sitting and standing.
• Improved level of alertness, attention, behavior regulation.
• Improved fine motor skills, such as hand pressure.
• Sound emission and contextual smile.
• Visual tracking, fixation and discrimination of auditory stimuli.

References

1. Ecured. (2016). Pallister-Killian syndrome. Obtained from Ecured.
2. Genetics Home Reference. (2016). Pallister-Killian mosaic syndrome. Obtained from Genetics Home Reference.
3. Inage et al. (2010). Phenotypic overlapping of trisomy 12p and PallistereKillian syndrome. European Journal of Medical Genetics, 159-161.
4. NORD. (2016.). Pallister Killian Mosaic Syndrome. Obtained from National Organization for Rare Disorders.